title: Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors.
abstract: OBJECTIVE
  Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized.
  
  
  METHODS
  We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families.
  
  
  RESULTS
  In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed.
  
  
  CONCLUSIONS
  The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.
authors.affiliation: HNPCC-register, Department of Gastroenterology, Faculty of Health Sciences, Hvidovre University Hospital, Copenhagen University, Kettegård allé, Hvidovre, Denmark.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Ketabi
authors.forename: Katarina
authors.initials: K
authors.lastname: Bartuma
authors.forename: Inge
authors.initials: I
authors.lastname: Bernstein
authors.forename: Susanne
authors.initials: S
authors.lastname: Malander
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Erik
authors.initials: E
authors.lastname: Björck
authors.forename: Susanne
authors.initials: S
authors.lastname: Holck
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein